E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Angioedema |
angioedema hereditario |
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E.1.1.1 | Medical condition in easily understood language |
Hereditary Angioedema |
angioedema hereditario |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019860 |
E.1.2 | Term | Hereditary angioedema |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of daily dosing of oral BCX7353 in subjects with HAE |
Evaluar la seguridad y tolerabilidad a largo plazo de la administración por vía oral de dosis diarias de BCX7353 en sujetos con Angioedema Hereditario |
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E.2.2 | Secondary objectives of the trial |
To assess the effectiveness (i.e., HAE attack frequency, severity and disease activity over time) of BCX7353 during long-term administration To evaluate quality of life during long-term administration of BCX7353 To evaluate subject’s satisfaction with medication during long term administration of BCX7353 |
Evaluar la efectividad (frecuencia de los ataques de AEH, gravedad y actividad de la enfermedad a lo largo del tiempo) de BCX7353 durante su administración a largo plazo Evaluar la calidad de vida durante la administración a largo plazo de BCX7353 Evaluar la satisfacción del sujeto con la medicación durante la administración a largo plazo de BCX7353 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and nonpregnant, nonlactating females 2. Subjects with Type I or II HAE who have participated in a BCX7353 efficacy study 3. Access to appropriate medication for the treatment of acute HAE attacks 4. Female participants must meet at least 1 of the following requirements: a. Be a woman of childbearing potential (defined as a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) who agrees to use at least an acceptable effective contraceptive method during the study and for a duration of 30 days after last dose of study drug. Female subjects who report being postmenopausal for ≤ 2 years and have a follicle stimulating hormone (FSH) ≤ 40 mIU/mL must agree to use at least an acceptable effective contraceptive method and (as proposed above) during study and for 30 days after the last dose of study drug. b. Be a woman of non-childbearing potential (defined as postmenopausal for > 2 years or having an FSH > 40 mIU/mL if postmenopausal ≤ 2 years or have had a hysterectomy, bilateral oophorectomy, or documented ovarian failure. Non-childbearing potential may also be demonstrated in the previous efficacy study). c. Be a woman declaring herself as either sexually abstinent or exclusively having female sexual partners. Abstinence in this study is defined as "true abstinence: when this is in line with the preferred and usual lifestyle of the subject." 5. Male subjects must comply with the following requirements through the end of the study: a. Subjects with female partners of childbearing potential (defined as postmenopausal ≤ 2 years or a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) must agree to utilize at least 1 acceptably effective contraceptive method. b. Male subjects who declare themselves as sexually abstinent are acceptable for the purposes of this study. Abstinence in this study is defined as “true abstinence: when this is in line with the preferred and usual lifestyle of the subject.” 6. Able to provide written, informed consent 7. In the opinion of the Investigator, the subject is able to adequately comply with all required study procedures for the duration of the study. The subject must demonstrate adequate compliance with all study procedures required including diary recording of HAE attacks |
1. Varones y mujeres no embarazadas, no lactantes. 2. Sujetos con AEH Tipo I o Tipo II que hayan participado en un ensayo de eficacia de BCX7353 3. Acceso a medicación adecuada para el tratamiento de ataques agudos de AEH 4. Acuerdo de utilizar métodos de anticoncepción eficaces y adecuados 5. Ser capaz de proporcionar documento de consentimiento informado por escrito 6. A consideración del/a Investigador/a, el sujeto deberá ser capaz de cumplir adecuadamente con todos los procedimientos del estudio que sean necesarios durante el periodo del estudio. El sujeto deberá demostrar un cumplimiento adecuado de todos los procedimientos del estudio necesarios, incluido el registro en el cuaderno de los ataques de AEH |
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E.4 | Principal exclusion criteria |
1. Pregnancy or breast feeding or planned pregnancy during the study period 2. Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject’s safety or ability to participate in the study 3. Discontinuation of study drug due to a hypersensitivity reaction to BCX7353 in a prior study. This includes subjects who had a rash of any severity identified as possibly, probably, or definitely related to active BCX7353 in the previous study 4. Dementia, altered mental status or any psychiatric condition, that would prohibit the understanding or rendering of informed consent or participation in the study 5. Clinically significant abnormal ECG including but not limited to, a QTcF > 470 msec for women, a QTcF > 450 msec for men, a PR > 220 msec (both sexes), or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping 6. Unacceptable noncompliance in the previous BCX7353 efficacy study as assessed by the Sponsor or Investigator 7. Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular disease 8. Known family history of sudden cardiac death. Family history of sudden death from HAE is not exclusionary 9. History of or current implanted defibrillator or pacemaker 10. Use of concomitant medications that are metabolized by CYP2D6, CYP2C9, CYP2C19, or CYP3A4 and have a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study, including those known to prolong the QT interval 11. Use of a medication that is transported by P-gp and has a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study 12. Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study 13. Calculated creatinine clearance (CLcr) of ≤ 60 mL/min or AST or ALT value ≥ 2 times the ULN reference range value at screening or at the last available visit prior to enrollment 14. Investigational drug exposure, other than BCX7353, within 30 days prior to the screening visit (or baseline if no screening visit) 15. History of severe hypersensitivity to any medicinal product, which was associated with non HAE-related swelling, a severe rash requiring treatment/hospitalization, or anaphylaxis 16. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > 3 units of alcohol/day) 17. For subjects undergoing a screening visit, a positive drugs of abuse screen (unless used as a medical treatment [e.g., with a prescription]) 18. For subjects undergoing a screening visit, current infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 19. Subjects with an immediate family relationship to either Sponsor employees, the Investigator or employees of the study site who are named on the delegation log 20. Subjects who are held in an institution by a government or judicial order |
1. Embarazo o lactancia o embarazo planeado durante el periodo del estudio. 2. Toda enfermedad con relevancia médica o historia médica que, en opinión del Investigador/a o Promotor/a, pudiera interferir con la seguridad o capacidad del sujeto para participar en el estudio 3. Suspensión de la administración del medicamento del estudio debido a una reacción de hipersensibilidad a BCX7353 en un estudio anterior. Este aspecto incluye sujetos que mostraron una erupción de cualquier gravedad identificada como posible, probable o definitivamente relacionada con BCX7353 activo en el estudio anterior. 4. Demencia, estado mental alterado o cualquier enfermedad psiquiátrica, que impidiera otorgar el consentimiento informado o participar en el estudio. 5. Electrocardiograma con anomalías médicamente relevantes, incluido pero no limitado a: a QTcF > 470 msec para mujeres, QTcF> 450 msec para varones, a PR > 220 msec (ambos sexos), o contracciones ventriculares y/o atriales prematuras más frecuentes de las normales, y/o agrupadas en dos o más 6. Incumplimiento inaceptable de los requisitos en el anterior estudio de eficacia de BCX7353, a consideración del Promotor o Investigador. 7. Toda historia de relevancia médica de angina de pecho, infarto de miocardio, desmayo, arritmias cardiacas de relevancia médica, hipertrofia ventricular izquierda, miocardiopatía, o cualquier otro trastorno cardiovascular. 8. Historia familiar conocida de muerte súbita por paro cardiorrespiratorio. La historia familiar de muerte súbita por AEH no es excluyente 9. Historia o implantación actual de desfibrilador o marcapasos 10. Empleo de medicaciones concomitantes, dentro de los 7 días siguientes a la consulta inicial o de referencia, o bien se planee comenzar a tomarla durante el periodo del estudio, que se metabolicen mediante CYP2D6, CYP2C9, CYP2C19 o CYP3A4, y que presenten un rango terapéutico reducido, incluidos los conocidos por prolongar el intervalo QT. 11. Empleo de medicación que sea transportada por la P-glicoproteína (P-gp) y presente un rango terapéutico limitado, dentro de los 7 días desde la consulta de referencia o se planifique su comienzo durante el estudio. 12. Cualquier anomalía en los parámetros de análisis de laboratorio que, a consideración del Investigador, sea significativa médicamente y relevante para este estudio. 13. Una depuración de la creatinina (CLcr) estimada de ≤ 60 mL/min o valor AST o ALT ≥ 2 veces el límite máximo del valor normal de referencia que haya sido obtenida durante la consulta de screening o en la última consulta disponible anterior a la participación. 14. Exposición a medicamento en investigación, distinto a BCX7353, dentro de los 30 días anteriores a la consulta de screening (o consulta de referencia si no hay consulta de screening). 15. Historia de hipersensibilidad grave a cualquier producto médico, que estuviera asociada a hinchazón no relacionada con AEH, erupción grave que requiera tratamiento/hospitalización, o anafilaxia. 16. Historia de abuso de alcohol o drogas durante el año anterior, o evidencia actual de dependencia o abuso de sustancias (ingesta auto-informada de bebidas alcohólicas > 3 bebidas alcohólicas/día) 17. Para sujetos que asistan a la consulta de screening, un resultado positivo en consumo de drogas (a menos que fueran utilizadas como tratamiento médico [es decir, con receta]). 18. Para sujetos que asistan a la consulta de screening, infección actual del virus de la hepatitis B (VHB), virus de la hepatitis C (VHC), o virus de la inmunodeficiencia humana (VIH). 19. Sujetos que posean una relación familiar cercana con cualquier empleado del Promotor, Investigador o personal del centro del estudio que sean nombrados en el registro del grupo de trabajo. 20. Sujetos institucionalizados por orden del gobierno o sentencia judicial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who discontinue BCX7353 due to a treatment-emergent AE The proportion of subjects with treatment-emergent SAEs The proportion of subjects with treatment-emergent AEs The proportion of subjects with treatment-emergent Grade 3 or 4 AEs The proportion of subjects with treatment-emergent, treatment related AE consistent with a drug rash The proportion of subjects with treatment-emergent Grade 3 or 4 laboratory abnormalities The proportion of subjects who receive a reduced dose due to tolerability issues |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Number and rate of HAE attacks Durability of response (attack rate trend over time) Number and proportion of days with angioedema symptoms Patient-reported outcomes (HAE disease-specific AE-QoL questionnaire scores and TSQM Global Satisfaction scores) Number of attacks requiring attack medication Discontinuations due to lack of efficacy Severity of attacks |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Macedonia, the former Yugoslav Republic of |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Patient Last Visit |
LPLV |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |